Trial Outcomes & Findings for Eribulin Mesylate and Everolimus in Treating Patients With Triple-Negative Metastatic Breast Cancer (NCT NCT02120469)

NCT ID: NCT02120469

Last Updated: 2022-07-05

Results Overview

DLT defined as an adverse event (AE) or abnormal laboratory value as at least possibly related to the study medication and meets any of the criteria per NCI CTCAE v4.0.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

First cycle on treatment, up to 21 days

Results posted on

2022-07-05

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level B1 everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5 mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5 mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	13	10	4
Overall Study COMPLETED	12	10	3
Overall Study NOT COMPLETED	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level B1 everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5 mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5 mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study HER-2/neu-amplified	1	0	1

Baseline Characteristics

Eribulin Mesylate and Everolimus in Treating Patients With Triple-Negative Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level B1 n=13 Participants everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 n=10 Participants 5mg everolimus; 1.4 mg/m\^2 eribulin mesylate Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 n=4 Participants 7.5mg everolimus; 1.4 mg/m\^2 eribulin mesylate Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=27 Participants Total of all reporting groups
ECOG performance status Ambulatory and capable of all selfcare but unable to carry out any work activities	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Age, Continuous	56 years n=5 Participants	52.5 years n=7 Participants	50.5 years n=5 Participants	55 years n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	10 Participants n=7 Participants	4 Participants n=5 Participants	27 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	10 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	18 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian/Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Unknown	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	13 Participants n=5 Participants	10 Participants n=7 Participants	4 Participants n=5 Participants	27 Participants n=4 Participants
ECOG performance status Fully active, able to carry on all pre-disease performance without restriction	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
ECOG performance status Restricted in physically strenuous activity but ambulatory and able to do work of a light nature	8 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	15 Participants n=4 Participants

PRIMARY outcome

Timeframe: First cycle on treatment, up to 21 days

Population: Number analyzed for DLT only include participants that are evaluable. A1: 1 participant was not evaluable due to progression prior to completion of first two cycles and 1 participant was not evaluable due to toxicity attributed to diabetes. A2: 1 participant was not evaluable due to HER2+ repeat biopsy. B1: 1 participant was not evaluable due to HER2+ repeat biopsy.

DLT defined as an adverse event (AE) or abnormal laboratory value as at least possibly related to the study medication and meets any of the criteria per NCI CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Dose Level B1 n=12 Participants everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 n=8 Participants everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 n=3 Participants everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Participants Experiencing a Dose Limiting Toxicity (DLT) (Phase I) and the Recommended Phase IB Dose (RP2D)	4 Participants	4 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: 2 participants (1 on dose level A2 and 1 on dose level B1) were not evaluable for response because they were determined to be HER2+ on repeat biopsy.

Progression determined using response evaluation criteria in solid tumors (RECIST) version 1.1 or showed clinical progression. RECIST criteria for progression includes: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions. Rates and associated 95% confidence limits will be estimated.

Outcome measures

Outcome measures
Measure	Dose Level B1 n=12 Participants everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 n=10 Participants everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 n=3 Participants everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Subjects With Disease Progression Using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Phase IB)	10 Participants	8 Participants	3 Participants

SECONDARY outcome

Timeframe: On treatment, 21 days per cycle up to 2 years

Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 3 or higher toxicities attributed to eribulin mesylate or everolimus.

Outcome measures

Outcome measures
Measure	Dose Level B1 n=13 Participants everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 n=10 Participants everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 n=4 Participants everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Participants With Grade 3 or Higher Toxicities (Phase IB)	8 Participants	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: 2 participants (1 on dose level A2 and 1 on dose level B1) were not evaluable for response because they were determined to be HER2+ on repeat biopsy.

RECIST Criteria: Complete Response (CR): Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Dose Level B1 n=12 Participants everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 n=10 Participants everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 n=3 Participants everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Best Response Using the RECIST (Phase IB) Partial Remission	5 Participants	3 Participants	1 Participants
Best Response Using the RECIST (Phase IB) Stable Disease	6 Participants	2 Participants	1 Participants
Best Response Using the RECIST (Phase IB) Progressive Disease	1 Participants	5 Participants	1 Participants

SECONDARY outcome

Timeframe: From start of treatment to death due to any cause, assessed up to 2 years

Kaplan Meier methods will be used to estimate the median and 95% confidence limits across all dose levels per protocol plan.

Outcome measures

Outcome measures
Measure	Dose Level B1 n=25 Participants everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Median Overall Survival (Phase IB)	8.3 months Interval 5.5 to Due to insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Form the date treatment begins until the first date on which recurrence, progression, or death due to any cause, assessed up to 2 years

Kaplan Meier methods will be used to estimate the median and 95% confidence limits over all dose levels per protocol plan.

Outcome measures

Outcome measures
Measure	Dose Level B1 n=25 Participants everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Median Progression Free Survival (Phase IB)	2.6 months Interval 2.1 to 4.0	—	—

Adverse Events

Dose Level B1

Serious events: 1 serious events

Other events: 13 other events

Deaths: 6 deaths

Dose Level A1

Serious events: 3 serious events

Other events: 10 other events

Deaths: 10 deaths

Dose Level A2

Serious events: 1 serious events

Other events: 4 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level B1 n=13 participants at risk everolimus 5mg; eribulin 1.1mg/m\^2; 10 mL dexamethasone mouthwash Patients receive 5mg everolimus PO QD on days 1-21 and 1.1 mg/m\^2 eribulin mesylate IV on days 1 and 8 and 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL oral solution, swish for 2 min and spit, 4 times daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A1 n=10 participants at risk everolimus 5mg; eribulin 1.4mg/m\^2 Patients receive 5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Dose Level A2 n=4 participants at risk everolimus 7.5mg; eribulin 1.4mg/m\^2 Patients receive 7.5mg everolimus PO QD on days 1-21 and 1.4 mg/m\^2 eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/13 • While on study, an average of 9 months	10.0% 1/10 • While on study, an average of 9 months	0.00% 0/4 • While on study, an average of 9 months
Gastrointestinal disorders Abdominal pain	0.00% 0/13 • While on study, an average of 9 months	0.00% 0/10 • While on study, an average of 9 months	25.0% 1/4 • While on study, an average of 9 months
Gastrointestinal disorders Mucositis oral	0.00% 0/13 • While on study, an average of 9 months	0.00% 0/10 • While on study, an average of 9 months	25.0% 1/4 • While on study, an average of 9 months
Infections and infestations Infections and infestations - other	0.00% 0/13 • While on study, an average of 9 months	0.00% 0/10 • While on study, an average of 9 months	25.0% 1/4 • While on study, an average of 9 months
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/13 • While on study, an average of 9 months	0.00% 0/10 • While on study, an average of 9 months	25.0% 1/4 • While on study, an average of 9 months
Respiratory, thoracic and mediastinal disorders Dyspnea	7.7% 1/13 • While on study, an average of 9 months	20.0% 2/10 • While on study, an average of 9 months	0.00% 0/4 • While on study, an average of 9 months

Other adverse events

Additional Information

Dr. Yuan Yuan

City of Hope

Phone: 626-359-8111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place